STABILITY MEASUREMENT OF OLIGONUCLEOTIDES IN SERUM SAMPLES USING CAPILLARY ELECTROPHORESIS

An in vitro stability study of unmodified and modified antisense oligo nucleotides in human serum was performed with a previously developed c apillary electrophoretic method using either micellar solution or enta ngled polymer solution depending on the oligonucleotide length to be s eparated. A method has been devised and validated for the extraction o f oligonucleotides from serum using anion-exchange centrifugal filter units. The extracted samples were desalted by a drop dialysis method. The serum half-lives and the degradation patterns of unmodified and mo dified oligonucleotides are compared. The modified oligonucleotide use d in this study is protected from exonuclease activity present in huma n serum by terminal 1,3-propanediol modification. (C) 1997 Elsevier Sc ience B.V.